Human Placental Lactogen Rises Through Pregnancy
hPL increases steadily from the placenta as gestation progresses.
- Placenta: Source (Syncytiotrophoblast cells)
- 3rd: Peak trimester (Late gestation rise)
- Lipolysis: Main effect (Frees maternal fatty acids)
- ↑ Linear: Trend (With placental mass)
hPL secretion pattern
Placenta secretes more hPL as it grows across gestation.
Progesterone Adds to Maternal Insulin Resistance
Progesterone works alongside hPL to reduce insulin sensitivity.
- Placenta: Source (Corpus luteum early on)
- Indirect: Receptor effect (Alters signaling cascade)
- With hPL: Synergy (Combined resistance effect)
- ↑ Steady: Trend (Rises with gestation)
Progesterone mechanism
Progesterone contributes modestly but steadily to resistance.
Insulin Receptor Signaling Is Blocked
Hormones interfere at the insulin receptor and post-receptor level.
- IRS-1: Site (Post-receptor substrate)
- Phosphorylation: Mechanism (Altered signaling cascade)
- Muscle/fat: Tissue (Reduced glucose uptake)
- ↓ Sensitivity: Result (Maternal cells resist insulin)
Blockade pathway
Hormone signaling disrupts normal insulin receptor cascade steps.
Physiologic Adaptation Versus Pathologic Resistance
Moderate resistance is normal; excessive levels become pathologic.
- Fetal fuel: Normal role (Shunts glucose to fetus)
- Variable: Threshold (Depends on baseline sensitivity)
- 24-28 wks: Screening (Oral glucose tolerance test)
- Hyperglycemia: Pathologic sign (Fasting/postprandial rise)
Where the line falls
Resistance becomes pathologic once compensation cannot keep pace.
Beta-Cell Compensation Failure Leads to GDM
Inadequate beta-cell output under rising resistance causes GDM.
- ↑ Insulin: Normal response (Beta-cells compensate)
- Limited reserve: Failure mode (Cannot meet demand)
- GDM: Outcome (Gestational diabetes mellitus)
- Prior history: Risk factor (Or reduced beta-cell mass)
Compensation failure
Limited capacity plus rising resistance together produce GDM.
Adequate beta-cell reserve largely offsets resistance and lowers GDM risk.